Table 1

The different molecular sub-phenotypes of cystic fibrosis

Mutation class	Defect	Exemplar mutations	Corrective therapy
I	Premature stop codon leading to a truncated transcript which is destroyed	G542X, W1282X	None available, compounds which override premature termination codons being explored Candidate for gene therapy
II	Abnormal protein is synthesised but destroyed, not trafficked to cell membrane	DF508	Corrector–potentiator combinations, e.g. Trikafta
III	Impaired anion conductance function	G551D	The potentiator ivacaftor
IV	Decreased channel opening time	R117H	The potentiator ivacaftor
V	Less CFTR protein reaches the cell surface	3849+10 kb C>T	Splicing correctors when available, possibly ivacaftor
VI	Protein is abnormally unstable at the cell surface	c.120del23	Promote stability when medications available
VII	No mRNA produced	1717-1G->A	No therapies available Candidate for gene therapy

Note that mutations may fall into more than one subcategory. For example, DF508, a class II mutation, is also unstable at the cell surface (class VI).